Regulation of Polyamine Biosynthetic Activity by Spermidine and Spermine Analogs — A Novel Antiproliferative Strategy

  • Carl W. Porter
  • Raymond J. Bergeron
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 250)

Abstract

Our current rationale for targeting polyamines as a mechanism-based drug discovery initiative is based on several diverse yet interrelated considerations (Table 1) some of which derive from findings to be reviewed here. Of these, the most critical are (a) the strict dependence of proliferating cells on polyamine availability (b) the increased rate of polyamine biosynthesis and transport associated with neoplastic tissues relative to their normal counterparts and (c) the novelty of polyamine biosynthesis and/or function as a departure from more cyto-toxic DNA-directed approaches. While admittedly, an absolute basis for selectivity has not yet been defined, recognition must be given to the fact that no chemotherapeutic strategy described to date is wholly selective for tumor tissue and yet total curability of a number of malignant diseases can be achieved. We believe this justifies the evaluation of new and novel approaches even in the absence of absolute metabolic rationale for selective tumor cell kill. Although still confined to animal model systems, encouraging antitumor data with polyamine analogs lend credence to this belief (Bergeron et al., 1988).

Keywords

Ethyl Propyl Ornithine Putrescine Phosphorylase 

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Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Carl W. Porter
    • 1
  • Raymond J. Bergeron
    • 2
  1. 1.Grace Cancer Drug CenterRoswell Park Memorial InstituteBuffaloUSA
  2. 2.Department of Medicinal Chemistry, J. Hillis Miller Health CenterUniversity of FloridaGainesvilleUSA

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